慢性胰腺炎患者血液免疫指標的檢測和分析

·論著·

慢性胰腺炎患者血液免疫指標的檢測和分析

鄭兆泓趙九龍杜婷婷胡良皞廖專葉博李白容季鈞淘王丹林金歡李兆申

【摘要】目的檢測慢性胰腺炎(CP)患者各項血液自身免疫指標的陽性率，探討其臨床價值。方法檢測上海長海醫院消化科就診的409例CP患者的抗可提取性核抗原抗體(抗ENA抗體)、抗胞漿型中性粒細胞抗體、抗β2-糖蛋白1抗體(anti-β2-GPI)、抗心磷脂抗體(ACA)、抗單鏈-DNA抗體等25項血清相關自身免疫指標，并與系統檢索的Pubmed數據庫內相關文獻的健康人群陽性率進行比較。結果409例CP患者中僅檢出anti-β2-GPI、ACA、抗雙鏈-DNA抗體陽性患者，陽性率分別為11.7%、1.4%、1.9%，其余指標均為陰性。其中anti-β2-GPI陽性率與健康人群相比有顯著提高(11.7%比3.4%)，ACA陽性率低于健康人群(1.4%比4.1%)，差異均有統計學意義(P值均<0.05)。而抗單鏈-DNA抗體陽性率與健康人群的差異無統計學意義。結論anti-β2-GPI對于CP的診療具有潛在價值，ACA的臨床意義尚不確定。

【關鍵詞】胰腺炎，慢性；自身免疫疾??；生物學標記；抗β2-糖蛋白1抗體

DOI:10.3760/cma.j.issn.1674-1935.2015.02.006

收稿日期：(2015-01-08)

Detection and analysis of blood immune parameters in patients with chronic pancreatitisZhengZhaohong,ZhaoJiulong,DuTingting,HuLianghao,LiaoZhuang,YeBo,LiBairong,JiJuntao,WangDan,LinJinhuan,LiZhaoshen.DepartmentofGastroenterology,ChanghaiHospital,SecondMilitaryMedicalUniversity,Shanghai200433,China

Correspondingauthor:LiZhaoshen,Email:zhaoshen-li@hotmail.com

Abstract【〗ObjectiveTo explore the positive rate of each autoimmunity parameters in patients with chronic pancreatitis. MethodsFour hundred and nine chronic pancreatitis patients treated in Department of Gastroenterology of Changhai Hospital were selected and the 25 autoimmunity parameters included anti-ENA antibody, anti-neutrophil cytoplasmic antibody, anti-β2-GPI, anticardiolipin antibody (ACA), anti dsDNA antibody were determined, then a literature search was performed to compare the autoimmune positive rate of healthy people in Pubmed database with chronic pancreatitis patients. ResultsAmong 409 patients, the positive rates of anti β2-GPI, ACA, and anti dsDNA antibody were 11.7%, 1.4%, and 1.9%, respectively, whereas other indicators were negatively expressed. The positive rate of anti β2-GPI in CP patients was significantly higher than that of healthy group (11.7%vs3.4%), and the positive rate of ACA was lower than that of healthy group (1.4%vs4.1%), and the difference between the two groups was statistically significant (P<0.05). ConclusionsAnti β2-GPI shows some potential value in the diagnosis and treatment of chronic pancreatitis, but the clinical significance of ACA is uncertain.

【Key words】Pancreatits, chronic;Autoimmune diseases;Biological markers;anti-β2 glycoprotein 1

慢性胰腺炎(chronic pancreatitis，CP)是胰腺的一種進行性炎癥性疾病。隨著國人生活水平的提高，CP的發病率有增長的趨勢，嚴重地影響了人們的工作和生活。目前關于CP的病因除了攝入酒精較為明確[1]外，其他致病因素尚不明確，影響了疾病的診斷和治療。自身免疫性胰腺炎(autoimmune pancreatitis, AIP)作為CP的一種亞型，自身免疫指標IgG4對于其診斷的價值已得到明確[2]。對于其他特發性CP患者，自身免疫因素是不是其致病因素，是否需要對CP患者行血液自身免疫指標檢測，目前尚無明確的相關研究。本研究檢測CP患者(AIP除外)的血液自身免疫指標，以明確CP與自身免疫是否相關。

作者單位：200433上海，第二軍醫大學長海醫院消化內科

通信作者：李兆申，Email: zhaoshen-li@hotmail.com

資料與方法

一、一般資料

選取2008年1月至2013年12月在上海長海醫院消化內科就診并同意接受檢測的CP患者(AIP與有免疫性疾病史除外)共409例，其中男性291例，女性118例，平均年齡(34±8)歲。青少年(<18歲)患者55例。

二、檢測指標

檢測的血指標包括抗可提取性核抗原抗體(抗ENA抗體)，抗SS-A，抗SS-B，抗JO-1，抗RNP，抗Scl-70，抗Sm，抗胞漿型中性粒細胞抗體，抗多發性肌炎硬皮病抗體，抗蛋白酶3抗體IgG，抗髓過氧化物酶抗體，抗線粒體M2抗體，抗核糖體抗體，抗腎小球基底膜抗體，抗增殖細胞核抗原抗體，抗β2-糖蛋白1抗體(anti-β2-GPI )，抗核小體抗體，抗組蛋白抗體，抗核周型中性粒細胞抗體，抗雙鏈-DNA抗體，抗單鏈-DNA抗體，抗核抗體，抗平滑肌抗體，抗線粒體抗體，抗心磷脂抗體(ACA)，免疫球蛋白G4亞型(IgG4)，共25項自身免疫指標。

三、對照組的設置

因本研究基于大樣本的臨床檢測，未設置相關對照組，且部分抗體在健康人群中陽性率的相關研究較少，并且尚無準確、統一的數值，故系統檢索Pubmed，選取庫內所有涉及健康人群相關自身免疫陽性率的文獻作為對照。例如以anti-β2 glycoprotein I和anti-β2-GPI作為關鍵詞檢索Pubmed數據庫，選取庫內所有涉及健康人群anti-β2-GPI陽性率的相關文獻共16篇[3-18]，anti-β2-GPI分為IgA、IgG、IgM3型，本次檢測為anti-β2-GPI總值，故單獨檢測anti-β2-GPI 3種分型之一的相關文獻未列入統計。

四、統計學處理

結　　果

一、CP患者血液自身免疫指標的陽性率

409例CP患者中48例患者的anti-β2-GPI呈陽性，陽性率11.7%。48名陽性患者中anti-β2-GPI的平均值為38.51RU/ml，預測他們的anti-β2-GPI 值分布在33.40～43.63RU/ml(95%CI)，明顯高于≤20RU/ml的正常參考值[19]。Pubmed數據庫內所有涉及健康人群anti-β2-GPI陽性率的相關文獻共16篇，納入2 438名健康者，其中88名陽性，陽性率為3.4%。CP 患者陽性率顯著高于文獻報道的健康人群，差異有統計學意義(χ2=50.85，P<0.001)。

本組6例患者ACA呈陽性，陽性率1.4%。數據庫涉及的健康人群陽性率的相關文獻共12篇[20-31]，納入7 269名健康者，其中299例陽性，陽性率為4.1%。CP患者陽性率顯著低于文獻報道的健康人群，差異有統計學意義(χ2=7.07，P<0.001)

本組8例患者抗雙鏈-DNA抗體陽性，陽性率1.9%。數據庫涉及健康人群的陽性率的相關文獻共5篇[32-36]，納入368名健康者，其中8名陽性，陽性率為2.1%。CP患者與健康人群的差異無統計學意義(χ2=0.01，P>0.05)。

其余22項自身免疫指標均未發現陽性者。

CP患者血anti-β2-GPI、ACA、抗雙鏈-DNA抗體的陽性率之間有相關性(F=29.33，P<0.001)。

二、anti-β2-GPI陰性與陽性CP患者的比較

anti-β2-GPI陽性CP患者胰腺發育異常(胰腺分裂、胰管匯流異常、環狀胰腺等)發生率高于陰性的CP患者，差異有統計學意義(P<0.05)，其他指標的差異均無統計學意義(表1)。

表1　anti-β2-GPI陰性與陽性CP患者的臨床資料比較

三、胰腺發育異常者與正常者的比較

23例CP患者存在胰腺發育異常。胰腺發育異常CP患者的男性占比低于胰腺發育正常的CP患者，血清anti-β2-GPI陽性率顯著高于胰腺發育正常的CP患者，差異均有統計學意義(P值均<0.05)，其他指標的差異均無統計學意義(表2)。

表2　胰腺發育異常與正常的CP患者的臨床資料比較

討　　論

本研究檢測了CP患者25項血清自身免疫指標，其中anti-β2-GPI、ACA、抗雙鏈-DNA抗體呈現陽性。CP患者的anti-β2-GPI陽性率高于健康人群，提示該指標與CP有相關性。anti-β2-GPI為肝細胞合成并影響甘油三酯和膽固醇的代謝，它還參與凝血過程，促進微血栓形成[37-39]。Wanless等[40]報道，肝微血栓的形成與肝臟纖維化相關。CP作為一種胰腺實質萎縮、纖維化的疾病，anti-β2-GPI引起微血栓形成亦可能與CP的胰腺纖維化相關。但anti-β2-GPI的檢測對于CP患者是否具有早期診斷的價值，其數值的變化是否具有評價疾病預后及判斷治療效果的價值都需要進一步研究證實。anti-β2-GPI在胰腺發育異常的患者中也顯著升高，提示該指標與胰腺發育異常的相關性。anti-β2-GPI檢測目前主要應用于習慣性流產，系統性紅斑狼瘡，腦卒中等疾病，其中在系統紅斑狼瘡的陽性率較高，其余疾病的陽性率大部分在10%～20%之間[3-18]，與本研究所得陽性率數值相近?？剐牧字贵w作為一種以血小板和內皮細胞膜上帶負電荷的心磷脂作為靶抗原的自身抗體，其陽性率增高常見于系統性紅斑狼瘡、血栓形成相關疾病、習慣性流產等。本研究該抗體陽性率低于健康人群，其原因尚不明確，有無臨床意義有待進一步探討?；谧陨砻庖咭蛩夭⒉皇荂P常見的致病因素，且全面篩查自身免疫指標費用較高，故對CP患者無需全面檢查各項免疫指標，僅檢測anti-β2-GPI單項指標即可。

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